PTP1B Inhibitory Secondary Metabolites from an Antarctic Fungal Strain

• Published in: Molecules
• Main Authors: Kim, Hye Jin, Li, Xiao-Jun, Kim, Dong-Cheol, Kim, Tai Kyoung, Sohn, Jae Hak, Kwon, Haeun, Lee, Dongho, Kim, Youn-Chul, Yim, Joung Han, Oh, Hyuncheol
• Format: Article in Journal/Newspaper
• Language: English
• Published: MDPI 2021
• Subjects: Acremonium sp.; Antarctic fungal metabolites; PTP1B; terpenoids; Antarc*; Antarctic
• Online Access: https://doi.org/10.3390/molecules26185505; https://pubmed.ncbi.nlm.nih.gov/34576982; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468024/

Chemical investigation of the Antarctic lichen-derived fungal strain Acremonium sp. SF-7394 yielded a new amphilectane-type diterpene, acrepseudoterin (1), and a new acorane-type sesquiterpene glycoside, isocordycepoloside A (2). In addition, three known fungal metabolites, (-)-ternatin (3), [D-Leu]-ternatin (4), and pseurotin A (5), were isolated from the EtOAc extract of the fungal strain. Their structures were mainly elucidated by analyzing their NMR and MS data. The absolute configuration of 1 was proposed by electronic circular dichroism calculations, and the absolute configuration of the sugar unit in 2 was determined by a chemical method. The inhibitory effects of the isolated compounds on protein tyrosine phosphatase 1B (PTP1B) were evaluated by enzymatic assays; results indicated that acrepseudoterin (1) and [D-Leu]-ternatin (4) dose-dependently inhibited the enzyme activity with IC50 values of 22.8 ± 1.1 μM and 14.8 ± 0.3 μM, respectively. Moreover, compound 1 was identified as a competitive inhibitor of PTP1B.